Dynamic Changes to the Skeletal Muscle Proteome and Ubiquitinome Induced by the E3 Ligase, ASB2β.

Ubiquitination is a posttranslational protein modification that has been shown to have a range of effects, including regulation of protein function, interaction, localization, and degradation. We have previously shown that the muscle-specific ubiquitin E3 ligase, ASB2β, is downregulated in models of muscle growth and that overexpression ASB2β is sufficient to induce muscle atrophy. To gain insight into the effects of increased ASB2β expression on skeletal muscle mass and function, we used liquid chromatography coupled to tandem mass spectrometry to investigate ASB2β-mediated changes to the skeletal muscle proteome and ubiquitinome, via a parallel analysis of remnant diGly-modified peptides.

Guidelines and scientifically-based spina bifida care: Guidance across the lifespan in a global health context.

The COVID-19 pandemic has reminded us that, if of nothing else, we live in a globalized community. Enthusiasm for evidenced-based medical knowledge is also contagious. Just as the incidence of SARS-CoV-2, the associated coronavirus, has had a borderless impact on global public health, so too neural tube defects have widespread significance.

TMEPAI/PMEPA1 Is a Positive Regulator of Skeletal Muscle Mass.

Inhibition of myostatin- and activin-mediated SMAD2/3 signaling using ligand traps, such as soluble receptors, ligand-targeting propeptides and antibodies, or follistatin can increase skeletal muscle mass in healthy mice and ameliorate wasting in models of cancer cachexia and muscular dystrophy. However, clinical translation of these extracellular approaches targeting myostatin and activin has been hindered by the challenges of achieving efficacy without potential effects in other tissues. Toward the goal of developing tissue-specific myostatin/activin interventions, we explored the ability of transmembrane prostate androgen-induced (TMEPAI), an inhibitor of transforming growth factor-β (TGF-β1)-mediated SMAD2/3 signaling, to promote growth, and counter atrophy, in skeletal muscle.

Nonfasted Liver Stiffness Correlates with Liver Disease Parameters and Portal Hypertension in Pediatric Cholestatic Liver Disease.

Elastographic measurement of liver stiffness is of growing importance in the assessment of liver disease. Pediatric experiences with this technique are primarily single center and limited in scope. The Childhood Liver Disease Research Network provided a unique opportunity to assess elastography in a well-characterized multi-institutional cohort.

Ethical and Regulatory Concerns in Pragmatic Clinical Trial Monitoring and Oversight.

The implementation of pragmatic clinical trials (PCTs) can be accompanied by unique regulatory challenges. In this paper, we describe the experience and management of regulatory noncompliance during a 25-site acute care PCT. During the trial, the study team conducted a comprehensive audit of all enrollment forms (informed consent and Health Insurance Portability and Accountability Act authorization forms) and related study documentation.

Healthy Aging Project-Brain: A Psychoeducational and Motivational Group for Older Veterans.

Introduction: Positive health behaviors can promote brain health with age. Although healthy lifestyle factors are often encouraged by health care providers, many older adults experience difficulty incorporating these into their daily life.

Methods: To address this gap, we developed a novel health education and implementation group for older veterans (aged > 50 years).

Correction: Chronic Granulomatous Disease-Associated IBD Resolves and Does Not Adversely Impact Survival Following Allogeneic HCT.

The original version of this article unfortunately contained the missing author, Caridad Martinez. The authors would like to correct the list. We apologize for any inconvenience that this may have caused.

Analyzing population structure for forensic STR markers in next generation sequencing data.

Match probabilities calculated during the evaluation of DNA evidence profiles rely on appropriate values of the population structure quantity θ. NGS-based methods will enhance forensic identification and with the transformation to such methods comes the need to facilitate NGS-based population genetics analysis. If NGS data are to be used for match probabilities there needs to be a way to accommodate population structure, which requires values for θ for those data.

Activated CD8 T-cell Hepatitis in Children With Indeterminate Acute Liver Failure: Results From a Multicenter Cohort.

Objectives: In many pediatric acute liver failure (PALF) cases, a diagnosis is not identified, and the etiology is indeterminate (IND-PALF). Our pilot study found dense CD8 T-cell infiltrates and increased T-cell clonality in liver specimens from IND-PALF patients. We aimed to validate these findings in a multicenter cohort with investigators blinded to diagnosis.

A study assessing the feasibility of randomization of pediatric and young adult patients between matched unrelated donor bone marrow transplantation and immune-suppressive therapy for newly diagnosed severe aplastic anemia: A joint pilot trial of the North American Pediatric Aplastic Anemia Consortium and the Pediatric Transplantation and Cellular Therapy Consortium.

Background: Recent data show survival after matched unrelated donor (MUD) bone marrow transplantation (BMT) is similar to matched sibling procedures for young patients with severe aplastic anemia (SAA). Donor delays, risk of transplant-related mortality (TRM), and concern about chronic graft versus host disease raise questions about whether MUD BMT or immune suppression therapy (IST) should be preferred initial therapy for young patients lacking matched sibling donors.

Procedure: We performed a pilot trial to assess the feasibility of randomizing patients under age 26 with newly diagnosed SAA to receive IST versus MUD BMT.

Shoulder Release and Tendon Transfer following Neonatal Brachial Plexus Palsy: Gains, Losses, and Midline Function.

Background: Shoulder release and tendon transfer is frequently performed to address persistent weakness from neonatal brachial plexus palsy. Although postoperative improvements in motion are well described, associated deficits are poorly documented, and functional assessments are lacking. Loss of ability to reach midline can occur with surgery and may result in impairment.

How Should Adolescent Health Decision-Making Authority Be Shared?

Shared decision making (SDM) is used in adult and pediatric practice for both its ethical and its practical benefits. However, its use is complicated with adolescents whose emerging and relational autonomy is distinct from that of adults, who make decisions independently, and children, whose parents make decisions for them. This hypothetical case scenario and commentary provide clinicians with a practical and stepwise approach to SDM with adolescents as well as guidance when SDM breaks down.

Diversity and Inclusion in Unregulated mHealth Research: Addressing the Risks.

mHealth devices and applications, with their wide accessibility and ease of use, have the potential to address persistent inequities in biomedical research participation. Yet, while mHealth technologies may facilitate more inclusive research participation, negative features of some unregulated use in research - misleading enrollment practices, the promotion of secondary mHealth applications, discriminatory profiling, and poorer quality feedback due to dependencies on biased data and algorithms - may threaten the trust and engagement of underrepresented individuals and communities. To maximize the participation of currently disenfranchised groups, those involved in unregulated mHealth research must become aware of potential risks, adopt targeted education policies, audit algorithms for hidden biases, and engage citizen scientists and other community members to identify and forestall possible harms.

The Multiple Sclerosis Surveillance Registry: A Novel Interactive Database Within the Veterans Health Administration.

Objective: To demonstrate the infrastructure and utility of an interactive health system database for multiple sclerosis (MS), we present the MS Surveillance Registry (MSSR) within the US Department of Veterans Affairs (VA).

Background: Disease specific databases can be helpful in the management of neurologic conditions but few are fully integrated into the electronic health record and linked to health system data. Creating a consistent information technology (IT) architecture and with ongoing support within disease specific registries has been a challenge.

The Group Practice Manager in the VHA: A View From the Field.

The Veterans Health Administration implemented the group practice manager position at 5 diverse prototype sites to improve clinical practice management and increase access to care.

Polysomnography outcomes of sleep endoscopy-directed intervention in surgically naïve children at risk for persistent obstructive sleep apnea.

Purpose: Drug-induced sleep endoscopy (DISE) is useful in children with obstructive sleep apnea (OSA) that persists after adenotonsillectomy (AT), but its utility in surgically naïve children is unclear. We report polysomnography outcomes of surgically naïve children who underwent DISE-directed intervention because they were considered high risk for persistent OSA after adenotonsillectomy.

Methods: This study is a case series of 62 surgically naïve children with OSA who were considered high risk for persistence after AT and underwent DISE-directed intervention with pre- and postoperative polysomnography between 2012 and 2016.

Immigration and transition: Changing demographics forecast the emerging trends in spina bifida care.

Globally, the number of immigrants, refugees, and internally displaced persons is escalating. While immigration is often a result of social determinants, including political discrimination, poverty, education, and work-related prospects, immigration itself can also be conceptualized as a social determinant of health. Through the National Spina Bifida Patient Registry (NSBPR), investigators have begun to recognize existing disparities within growing minority populations affected by spina bifida.

Potential Unintended Consequences Of Recent Shared Decision Making Policy Initiatives.

Shared decision making (SDM)-when clinicians and patients make medical decisions together-is moving swiftly from an ethical ideal toward widespread clinical implementation affecting millions of patients through recent policy initiatives. We argue that policy initiatives to promote SDM implementation in clinical practice carry the risk of several unintended negative consequences if limitations in defining and measuring SDM are not addressed. We urge policy makers to include prespecified definitions of desired outcomes, offer guidance on the tools used to measure SDM in the multitude of contexts in which it occurs, evaluate the impact of SDM policy initiatives over time, review that impact at regular intervals, and revise SDM measurement tools as needed.

Participant Engagement in Translational Genomics Research: Respect for Persons-and Then Some.

The expansion of both formal and informal frameworks of "engaged" research in translational research settings raises emerging and substantial normative concerns. In this article, we draw on findings from a focus group study with members of a national consortium of translational genomic research sites. The goals were to catalog informal participant engagement practices, to explore the perceived roots of these practices and the motivations of research staff members for adopting them, and to reflect on their ethical implications.

An enhanced recovery after surgery pathway for cesarean delivery decreases hospital stay and cost.

Background: Enhanced recovery after surgery pathways provide a multidisciplinary, evidence-based approach to the care of surgical patients. They have been shown to decrease postoperative length of stay and cost in several surgical subspecialties, including gynecology, but have not been well-studied in obstetric patients who undergo cesarean delivery.

Objective: We sought to determine whether the implementation of an enhanced recovery after surgery pathway for cesarean delivery would decrease postoperative length of stay and postoperative direct cost compared with historic controls.

Longitudinal Study Comparing Pulpectomy and Pulpotomy Treatments for Primary Molars of Alaska Native Children.

The purpose of this study was to determine which pulp treatment technique, performed at the Alaska Native Medical Center, is most successful by comparing failure rates of primary molars treated with ferric sulfate (FS) pulpotomy, sodium hypochlorite (SH) pulpotomy or pulpectomy between January 2005 and January 2016. All data were abstracted from the dental records of Alaska Native children aged 2-13 years, retrospectively. Clinical and radiographic failures up to five years after treatment were assessed.

Robotic-Assisted Bladder Neck Procedures for Incontinence in Pediatric Patients.

To review the current status of bladder neck procedures for incontinence in pediatric patients, focusing on the increasing role of robotic-assisted laparoscopic surgical techniques. A comprehensive review of the literature on open and robotic-assisted bladder neck procedures was conducted, with a focus on articles published in the last 20 years. This data was subsequently compared with published results from robotic-assisted bladder neck reconstruction series completed at our institution.